Osel was founded to develop and commercialize a novel approach to prevent vaginal HIV transmission. We propose to colonize the vaginal mucosa with non-pathogenic lactobacilli, genetically modified to bind and inactivate HIV. We are constructing recombinant lactobacilli that express the potent HIV-inhibitor, cyanovirin-N (CV-N), or related HIV binding proteins. The strain of lactobacillus, L. jensenii, is an excellent human vaginal colonizer and we have gained preliminary evidence that we can manipulate this strain to express foreign proteins on the bacterial surface. We are using a new, strong, lactobacillus-specific promoter to drive expression of CV-N as a surface-anchored or secreted protein. Thus, the expression of this potent HIV-inhibitor from the modified bacteria should reduce or eliminate HIV particles introduced by semen, thereby significantly reducing the risk of HIV transmission. This approach would be discrete, female-controlled and should act synergistically with vaccines, condoms or other potential methods of protection. The work being proposed by Osel includes the genetic modifications of L. jensenii and demonstration that the bioengineered bacteria are capable of blocking HIV-infectivity in vitro. PROPOSED COMMERCIAL APPLICATION: New approaches to block the transmission of viruses, like HIV, are urgently needed. The novel aproach proposed by Osel Inc. would find direct utility as a method to block HIV transmission. Since it is anticipated to be cost-effective, it can be used throughout the world, including in underdeveloped countries. The product will be marketed as a vaginal suppository to be used on a weekly, or monthly basis, and will be convenient to use and female-controlled. Importantly, the studies proposed in this application relate directly to a product concept associated with an unmet medical need and substantial commercial opportunity.